Three dimensional structure of proteins Flashcards
What are polypeptide bonds?
- covalent linkages between amino acids
- form by condensation reactions, loss of water molecule (eliminates alpha carboxyl and amino group)
- independent of the amino acids being joined
Residues:
Context of them being a peptide or polypeptide (residue 1: first amino acid)
Main chain:
Constant portions, everything except side chains
(side chains are variables)
Common pattern NCCNCC
Partial double bond characteristics:
- Rotation around C-N peptide bond is restricted
- six atoms of the peptide group are rigid and planar
- creates cis-trans isomers
Resident structures:
Double bond can be shared (partial double bond characteristics:
- Lose freedom of rotating
- rigid and planar
- limit flexibility
Configuration of Peptide bonds:
- peptide bonds tend to be in the trans configuration
- oxygen of the carbonyl and hydrogen of the amide group are usually trans to each other
Why isn’t the cis configuration favoured for Peptide bonds?
- the cis configuration is more likely to cause steric interference between side chains
- usually proline residues if cis
What are the four levels of protein structure?
- Primary Structure
- Secondary Structure
- Tertiary Structure
- Quaternary Structure
Steric exclusion
Two groups can’t occupy the same space at the same time
Primary Structure
Linear sequence of amino acids (tells you identity of amino acids and order, not position)
- Start at the N (amino) terminus and end at C (carboxyl) terminus
-cannot predict three-dimensional structure
Secondary Structure
localized patterns of folding in a polypeptide
- maintained by hydrogen bonds between main-chain amide and carbonyl groups
- include alpha helices and beta sheets
-maintain same overall characteristics
What are the two rules of secondary structure?
- they must optimize hydrogen bonding potential of main-chain carbonyl and amide groups (anything that can form a hydrogen will form one)
- They must represent a favoured conformation of the polypeptide chain (has to be allowed folding pattern)
Main chain hydrogen bonding groups (secondary structure):
- Each peptide bond has a hydrogen bond donor (amide) and acceptor (carbonyl) groups
- always going to have same number of acceptors and donors
- important for optimizing hydrogen bonds
What are Phi and Psi bonds?
Alpha carbons in main-chain through single bonds that have complete freedom of rotation (can range from -180 to 180)
Phi: angle between the alpha carbon and nitrogen atom
Psi: angle between alpha carbon and carbon of carbonyl group
Alpha helix wrapping conformation:
- wraps around axis in a right handed manner with 4 residues/turn
Which way does the alpha helix point to?
- N terminal (amide) to c terminal (carbonyl)
- positive to negative
What amino acids are usually not found in alpha helixes?
Proline: too rigid
Glycine: flexibility makes it wobbly
Side chains of Val, Thr, Ile: due to steric interference
Ser, Asp, Asn near main chain: ones with hydrogen bonding near main-chain
Charged residues: tend to be positioned to form favourable ion pairs (residues of opposite charge separated by 3-4 positions)
Why do the N and C terminuses have charges?
Every peptide bond has a small electrical dipole (gives the helix a net dipole)
- The longer and the more you have in a line the more polar and stronger the dipole is
- want to neutralize ends
How is the dipole of a helix stabilized?
Residues are put at each termini whose charge oppose the helix dipole
N terminus: negatively charged residues (Asp, Glu)
C terminus: positively charged residues (Lys, Arg, His)
There are two different faces of a helix:
- hydrophobic (non-polar) side
- Hydrophilic (polar) side
Beta sheets
- involves multiple beta strands arranged side by side
- often 4 or 5 strands
- fully extended polypeptide chains
Three types of beta sheets:
Parallel: strands run in the same direction (more flexible)
Anti-Parallel: strands run in opposite direction (more stable and stronger)
Mixed: contain both parallel and antiparallel
Amphipathic beta sheets
- side chains alternate above and below the polypeptide chain (alternate polar on one side and non-polar on the other)
Tertiary structure:
- final folding pattern of a single polypeptide chain
- Native conformation: biologically active form
- amino acid sequence determines tertiary structure
- can be made up of a bunch of weak interactions but makes an overall stable protein
How is energy involved in the tertiary structure?
- protein conformation with the lowest free energy (the most stable) is usually the one with the maximum number of weak interactions
- stability reflects difference in free energies of folded and unfolded (what you started with vs what you end up with; protein has to find the most stable structure)
Folding of proteins (tertiary):
- can be imagined as funnel, going from large number of unstable conformations and collapses into stable folding (rapid)
- goes from a higher entropy (randomness) to a low energy state of great stability
- some spontaneously fold some need chaperones
Chaperones
assist in the help of folding a protein
Denaturization
disruption of native conformation with loss of biological activity (the unfolding of a protein)
- energy needed for process is often small
- all or nothing: either going to fold properly or unfold
What are the 3 characteristics of denaturation?
- rapid
- cooperative process (once it starts to fall apart it all falls apart)
- reversible (spontaneously fold back into position; no energy required)
Quaternary Structure
Multiple subunits, each is a separate polypeptide
- could be same polypeptides or different ones
- subunits associate through noncovalent interactions (most important force stabilizing protein)
- more complex biological function
What are some biological advantages with quaternary structures?
- help stabilize subunits and prolong protein’s life
- Unique active sites at interfaces between proteins
- unique and dynamic combinations of structure/function through physiological changes in tertiary/quaternary structure (hemoglobin)
What are the biological roles of proteins?
- enzymes
- storage and transport
- physical cell support and shape
- mechanical movement
- decoding cell information
- hormones and hormone receptors (insulin)
- many other (antibodies)
Protein size
- difference in proteins depend on the length
- typically 100 to 1000 acids in length
- largest protein discovered is Titin
